The overall purpose of the NIH Pathway to Independence Award K99/ROO application is to provide a year of support for the mentored phase that is crucial in completing the critical testing of four hypotheses, followed by manuscript submission to relevant journals. The subsequent 3 year independent phase is necessary to establish my research program and reaching my goals as a junior faculty member. It would enable me to establish myself as an independent investigator in biomaterials integration and characterization taking into account both human and comparable animal tissues, subsequently building tissues with well optimized bioengineered interfaces. This award will enable me to study the proposed specific aims defined in this proposal and expand my knowledge on building the next generation materials for tissue regeneration. The thrust of these efforts is based on a general hypothesis that the functional biomechanics of a tooth are derived from structural and chemical interactions of its different components at several hierarchical levels (macro-, micro- and nano-scales), and that these yield properties that depend on location, age, and gender. Destruction of tissues including the periodontal ligament (PDL), cementum, and bone can cause loss of teeth due to periodontitis. Key challenges include 1). Understanding degradation of the tissues associated with disease progression, and 2). Regeneration of the interfaces that bind the oral tissues together. To address the first challenge, an animal model for periodontitis will be developed and the sequential degeneration of tissues determined by studying their structure, chemical composition and mechanical properties. For the second challenge, tissue engineering (TE) can be used to create novel scaffolds. However, a major limitation of current TE procedures is limited knowledge of scaffold biomechanics. An efficient scaffold should sustain functional loads in addition to providing an environment conducive to desired cell behavior. To address these challenges, the inherent characteristics of the tissues and their interfaces must be determined. Then, they can be mimicked using TE to create appropriate scaffolds. Hence the following specific aims are defined to: 1). Investigate structure, chemical composition, mechanical properties of primary and secondary cementums, 2). Investigate structure, chemical composition, mechanical properties of cementum and its interface with root dentin, 3). Investigate strain fields using functional loads on anterior and posterior teeth as a function of age, 4). Perform a comparison studies between structure, chemical composition and mechanical properties of healthy human and rat alveolar bone, PDL, cementum, root dentin and their bimaterial interfaces. This information will be used to determine chronological changes in structure, chemical composition and mechanical properties in the rat periodontal tissues and their bimaterial interfaces during disease progression.